Steroid receptor proteins appear to be regulatory molecules that interact with the cell's genetic material to control gene expression. Some human mammary tumors contain significant amounts of the estradiol receptor, and it is these tumors that respond to various endocrine therapies with remission of tumor growth. We wish to know more about the nature of the nuclear form of the receptor protein and more particularly, what kind of interaction it show with chromatin, and how hormone analogues may affect this interaction. We have shown that when estradiol is fed to isolated rat uteri or MCF-7 cells, a line of human mammary tumor cells, it binds to chromatin. This estradiol is prferentially released from the chromatin by digestion with various nucleases with the concomitant production of hormone-bound nucleosomes and hormone-receptor complex bound to a fragment of DNA. Transcriptionally active fractions of chromatin are enriched in estradiol. We now wish to determine: 1. whether nucleosomes containing estradiol otherwise differ from the bulk nucleosomes, i.e., whether we can detect the presence of special "acceptor" proteins or unique DNA sequences; 2. whether the components of active chromatin are different from those of the bulk chromatin; 3. whether steroid receptors occur in patchers or singly along the chromatin; 4. whether antiestrogens show similar binding to chromatin, or alter the binding of estradiol; 5. whether this binding is affected by thyroid hormone which is known to modulate the estradiol response in some tissues, and for which MCF-7 cells have been shown to have receptors; 6. whether progesterone shows binding characteristics similar to estradiol; and 7. whether different clones, or mutants of MCF-7 cells show different responses to steroid treatment and, if so, whether the interaction of their receptors with chromatin will differ from that occurring in wild type cells.